GDF11 Improves Ischemia-Reperfusion-Induced Acute Kidney Injury via Regulating Macrophage M1/M2 Polarization.

INTRODUCTION: Acute kidney injury (AKI) is a clinical emergency caused by the rapid decline of renal function caused by various etiologies. Growth differentiation factor 11 (GDF11) can promote renal tubular regeneration and improve kidney function in AKI, but the specific mechanism remains unclear. Herein, we investigated the effect and mechanisms of GDF11 in ameliorating AKI induced by ischemia-reperfusion (I/R). METHODS: An animal model of AKI was established by I/R method, and the changes of serum urea nitrogen and creatinine were measured to evaluate the AKI. Enzyme-linked immunosorbent assay (ELISA) was used to measure cytokines, malondialdehyde, superoxide dismutase, nitric oxide synthase, and arginase 1 levels. Flow cytometry was used to count the M1/M2 macrophages. IHC, WB, and q-PCR experiments were used to evaluate the expression of GDF11. RESULTS: The changes in serum levels of urea nitrogen and creatinine after I/R suggest that an animal model of AKI induced by I/R was successfully established. AKI caused by I/R significantly changed the M1/M2 macrophage polarization balance, with an increase in M2 being significantly higher than M1 as well as increased oxidative stress. Treatment with GDF11 after I/R significantly increased the differentiation of M2 cells and inhibited the differentiation of M1 macrophages, as well as decreased oxidative stress. CONCLUSION: GDF11 can promote the repair of AKI caused by I/R by regulating the balance of M1/M2 polarization in macrophages and oxidative stress.

Prediction model for cardiovascular disease risk in hemodialysis patients.

PURPOSE: To derive and validate a prediction score for cardiovascular disease (CVD) risk in hemodialysis patients in China. METHODS: Three hundred and eighty-eight patients with regular hemodialysis for more than 3 months were recruited from January 1, 2015 to September 30, 2019 and followed up till May 31, 2020. We derived a prediction score using all participants as a training data set and validated using a bootstrap validation data set. Discriminatory ability of the prediction score was assessed by the area under the receiver operating characteristic curve (AUC). RESULTS: Of 388 patients without CVD at baseline, 132 developed first CVD events during an average follow-up of 3.27 (inter-quartile range = 3.08) years. Of 26 clinical parameters, age, hypertension, diabetes and abnormal white blood cell (WBC) count were identified as significant predictors and included in the prediction model. Compared to those without any of these risk factors, those with one, two, and three to four points showed increased risks of CVD, with the adjusted hazards ratio and 95% confidence interval (CI) being 3.29 (1.17-9.26), 7.42 (2.68-20.51) and 15.43 (5.44-43.75), respectively. The score showed satisfactory discriminatory ability in both training and validation data set (AUC = 0.7025, 95% CI 0.6520-0.7530, and 0.6876, 95% CI 0.6553-0.7200, respectively). CONCLUSION: We derived and validated a prediction score for CVD risk in hemodialysis patients in China. Given there is a rapid increase in the number of hemodialysis patients, this simple point score can be used to identify high-risk individuals in clinical practice for more precise and efficient personalized treatment.

High-Sensitivity C-Reactive Protein Leads to Increased Incident Metabolic Syndrome in Women but Not in Men: A Five-Year Follow-Up Study in a Chinese Population.

PURPOSE: Metabolic syndrome (MetS), characterized by a constellation of insulin resistance, central obesity, hypertension, and hyperlipidemia, is a global health threat. High-sensitivity C-reactive protein (hs-CRP) has been shown to be associated with type 2 diabetes and cardiovascular disease; however, its association with incident MetS is less known. Therefore, the aim of this study was to examine the prospective association between hs-CRP and MetS among a Chinese population in a 5-year follow-up study. PATIENTS AND METHODS: The levels of hs-CRP were measured using serum samples collected at baseline recruitment in 2012 from 886 participants without MetS. Follow-up interviews were conducted in 2018, and MetS was diagnosed by 2017 criteria from the Chinese Diabetes Society. Multivariate logistic regression models were used to assess the overall and sex-specific associations between hs-CRP and incident MetS. The odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were computed with adjustment for demographic, socioeconomic, clinical, and lifestyle factors. RESULTS: After a mean follow-up duration of 5.40 ± 0.56 years, 116 (13.3%) participants developed MetS. In the total study population, increased hs-CRP levels were associated with a higher risk of MetS (OR comparing extreme quartiles of hs-CRP: 4.06 [95% CI: 1.91-8.65]) in the fully-adjusted model. When stratified by sex, the positive association was only observed in women (OR: 4.82 [1.89-12.3]) but not in men (OR: 3.15 [0.82-12.1]; P-interaction = 0.039). CONCLUSION: In this study of a Chinese population, a positive association between hs-CRP and incident MetS was found only in women and not in men. Sex-specific prediction and intervention of MetS using hs-CRP as a target should be further evaluated.

Urinary Extracellular Vesicle: A Potential Source of Early Diagnostic and Therapeutic Biomarker in Diabetic Kidney Disease.

OBJECTIVE: Diabetic kidney disease (DKD) has become one of the major causes of end-stage renal disease. Urinary extracellular vesicles (uEVs) contain rich biological information which could be the ideal source for noninvasive biomarkers of DKD. This review discussed the potential early diagnostic and therapeutic values of proteins and microRNAs in uEVs in DKD. DATA SOURCES: This review was based articles published in PubMed, Embase, Cochrane, and Google Scholar databases up to November 20, 2017, with the following keywords: "Diabetic kidney disease", "Extracellular vesicle", and "Urine". STUDY SELECTION: Relevant articles were carefully reviewed, with no exclusions applied to the study design and publication type. RESULTS: There is no "gold standard" technology to separate and/or purify uEVs. The uEVs contain a variety of proteins and RNAs and participate in the physiological and pathological processes of the kidney. UEVs, especially urinary exosomes, may be useful biomarkers for early diagnosis and treatment to DKD. Furthermore, the uEVs has been used as a therapeutic target for DKD. CONCLUSION: Proteins and nucleic acids in uEVs represent promising biomarker for the diagnosis and treatment of DKD.

[Association of waist-to-hip ratio with insulin resistance in non-diabetic normal-weight individuals: a cross-sectional study].

OBJECTIVE: To explore the relationship between waist-to-hip ratio (WHR) and insulin resistance(IR) in non-diabetic normal-weight individuals and investigate how this association differs between male and femalesubjects. METHODS: From June to October, 2012, we performed a cross-sectional survey among 2142 community-based non-diabetic Chinese participants, who were divided into 4 groups according to the gender-specific quartiles of WHR. Homeostatic model assessment of insulin resistance (HOMA-IR), calculated as the product of fasting plasma glucose (mmol/L) and fasting insulin (mU/L) divided by 22.5, was used as the indicator of insulin resistance. Logistic regression models were used to explore the association of WHR with IR in these subjects. RESULTS: In the unadjusted model, WHR was significantly associated with IR in women (OR=6.60, 95%CI: 2.86-15.26, P<0.001); the association was still significant (OR=3.28, 95%CI: 1.34-8.04, P=0.009) after adjustment for the potential confounders including the history of hypertension, coronary heartdisease, current smoker, physical inactivity, and body mass index. CONCLUSION: WHR is independently associated with IR in non-diabetic Chinese women with normal body weight.

[Association between hypertriglyceridemic waist?to?height ratio phenotype and chronic kidney disease in a community population in South China: a cross-sectional study].

OBJECTIVE: To investigate the relationship between hypertriglyceridemic waist to height ratio phenotype (HWHtR) and chronic kidney disease (CKD) in a community population in South China. METHODS: A cross sectional study was conducted among 2142 residents in Zhuhai (Guangdong Province, China) from June to October of 2012. The HWHtR phenotype was defined as a waist to height ratio(WHtR) ≥0.55 and triglyceride level ≥2.0 mmol/L, based on which the participants were divided into HWHtR group and nonHWHtR group. CKD was defined as an eGFR<60 mL/min per 1.73 m2 or an ACR ≥30 mg/g. A logistic regression model was established to investigate the relationship between chronic kidney disease and HWHtR phenotype. RESULTS: Compared with the nonHWHtR group, the HWHtR group had a higher prevalence of chronic kidney disease (11.1% vs 33%, P<0.001). Analysis using the logistic regression model showed that HWHtR was significantly associated with CKD in the unadjusted analyses (OR=3.23, 95% CI: 2.32-4.48, P<0.001). After adjustment for age, sex, history of hypertension, history of diabetes, systolic blood pressure, diastolic blood pressure, drinking, physical exercise, education and current smoking, HWHtR was significantly associated with CKD (OR=2.36, 95% CI: 1.52-3.67, P<0.001); the association of HWHtR and CKD was still significant after further adjustment for BMI (OR=2.12, 95%CI: 1.34-3.35, P<0.001). CONCLUSION: Our finding suggests that HWHtR is associated with CKD in this community population.

[Clinical and pathological features in IgA nephropathy with IgG deposition in the glomerular mesangial area].

OBJECTIVE: To investigate the relationship between the clinical and pathological findings in IgA nephropathy with or without IgG deposition in the glomerular mesangial area. METHODS: The data were collected from 122 patients with a diagnosis of IgA nephropathy by renal biopsy in the Third Affiliated Hospital of Southern Medical University between November, 2009 and February, 2016. All the samples were examined by light microscopy, immunofluorescence and electron microscopy. According to the results of immunofluorescence assay, the patients were divided into IgA group (n=63) and IgA-IgG group (n=59). The pathological classification of IgA nephropathy was analyzed according to Oxford classification and Lee's classification. The clinical and pathological findings were compared between the two groups. RESULTS: Compared with the patients with IgA nephropathy but without IgG deposition, patients with IgA nephropathy with IgG deposition had higher serum creatinine, higher 24-h urine protein, higher blood uric acid, higher triglyceride levels (P<0.05) and lower eGFR (P<0.05); more of these patients were in Lee's grade IV-V, had renal tubular atrophy and/or interstitial fibrosis, and had MEST scores more than 3 (P<0.05). CONCLUSION: Patients with IgA nephropathy with IgG deposition in the glomerular mesangial have severer clinical symptoms and more serious pathological changes. Measures should be taken to control IgG deposition in patients with IgA nephropathy to delay the progress of the disease.

[Association of waist-to-hip ratio with chronic kidney disease in non-diabetic subjects].

OBJECTIVE: To explore the relationship between waist-to-hip ratio (WHR) and chronic kidney disease (CKD) in non-diabetic subjects and compare the difference between male and female subjects. METHODS: We performed a cross-sectional survey among 2142 community-based southern Chinese participants without diabetes from June to October 2012. We divided all the participants into 4 groups according to the gender-specific quartiles of WHR. Logistic regression models were used to explore the associations of WHR with CKD in these subjects. RESULTS: In the unadjusted model, WHR was significantly associated with CKD in women (OR=7.29, 95% CI: 3.56-16.32, P<0.001), and the association was still significant (OR=6.13, 95% CI: 2.56-15.20, P=0.003 ) after adjustment for the potential confounders (including age, history of hypertension, coronary heart disease, current smoker, physical inactivity, education level, systolic blood pressure, diastolic blood pressure, serum triglyceride, serum high density lipoprotein, blood glucose, and BMI). The odds ratio (OR) for having CKD in the highest versus lowest quartile of WHR levels was 2.44 (95% CI: 0.98-4.97, P=0.103) in men in the unadjusted model. CONCLUSION: WHR levels are associated with CKD in non-diabetic women but not in non-diabetic male subjects.

[Expression of matrix metalloproteinase-9 in renal tissues of rats with chronic allograft nephropathy at early stage and the role thereof].

OBJECTIVE: To investigate the expression of matrix metalloproteinase-9 (MMP-9) in the renal tissues of rats with chronic allograft nephropathy (CAN) at early stage and its role in CAN. METHODS: Orthotopic transplantation of left kidney was performed between 10 male LEW rats and 10 male F344 rats with the formers as recipients. Small dose cyclosporin A was used to suppress acute rejection. Ten days after the operation the right kidneys of the recipients were resected. Ten LEW rats and 10 F344 rats with their single kidneys resected were used as controls. Twelve weeks after the operation the rats were harvested to take out the transplanted kidneys to undergo histologic examination. Immunochemistry was used to examine the expression of MMP-9 protein and transforming growth factor (TGF)-beta1 . RT-PCR was used to examine the expression of MMP-mRNA in the kidney tissues. At the same time 24 h urine samples were collected to examine the urinary protein. The relationship between the expression of MMP-9 and TGF-beta1 and the quantity of SMCs and mononuclear cells. RESULTS: The 24 h urinary protein level of the experimental group was not significantly different from those of the F3244 control group and LEW control group. The serum inosine level of the experimental group was significantly higher than that of the F334 control group and was not significantly different from that of the LEW control group. The degrees of pathologic change degree (Banff score) and fibrosis of kidney interstitium, and the number of inflammatory cells infiltrating into tubulointerstitium, arterial smooth muscle cells (SMCs) in renal cortex, and SMCs in vascular wall of the experimental group were all significantly higher than those of the 2 control groups. The expressions of MMP-9 protein and TGF-beta1 in the kidney interstitium and vascular wall and the expression of MMP-9 mRNA were all significantly higher than those of the 2 control groups. The expression of MMP-9 mRNA in kidney tissues was positively correlated with the degree of infiltration of interstitial mononuclear cells. The MMP-9 mRNA expression level was positively correlated with the number of interstitial mononuclear cells. The MMP-9 protein expression level was positively correlated with the TGF-beta1 expression level in the tubulointerstitium and in the renal arterial wall. CONCLUSION: MMP-9 plays a key role in CAN at early stage. Its expression may be induced by TGF-beta1.

[A pilot study of using pure albumin as a dialysate in the treatment of liver failure].

OBJECTIVE: To observe the effect of a new extracorporeal hepatic support-hemodialysis with albumin-based dialysate on patient with liver failure, and to compare the result with that of molecular absorbent recycling system (MARS). METHODS: Eighteen patients with liver failure were enrolled and treated intermittently with artificial liver on the basis of conventional regime. Among them, 12 of them were treated with single albumin dialysis (SAD) for 6 hours each period, and 6 with MARS for 6 hours. During each session of SAD, 4,000 ml albumin-based dialysate (45 g/L) was circulated in the dialysate route at a flow rate of 10 L/h with the blood flow rate of 250 ml/min. Liver and renal function, prothrombin activity (PTA), serum ammonia (NH(3)), endotoxin were monitored before and after the treatment, and the serial bilirubin content was measured in the serum and the albumin dialysate of all patients respectively 1-hour, 3-hour, 6-hour after the treatment with SAD. RESULTS: After treatment with SAD, the clinical symptoms and signs were improved and the hemodynamics were stabilized, complications were ameliorated partially, in particular hepatic encephalopathy was improved, with low incidence of adverse reaction, and the effective rate and survival rate were high. The serum PTA was increased obviously (P<0.05), and the serum blood urea nitrogen (BUN), serum creatinine (SCr), total bilirubin (TB), total bile acid (TBA), NH(3), endotoxin were decreased significantly (all P<0.05), and elimination of bilirubin slowed down gradually. The results showed that SAD was as effective as MARS, with a lower cost, and simpler and more convenient than MARS. CONCLUSION: Single albumin dialysis may eliminate protein-bound and water-soluble hepatic toxins, improve clinical symptoms and liver function in the treatment of liver failure, and worth further clinical study.

[Detection of PLA2R1 in renal biopsy specimens of patients with idiopathic membranous nephropathy].

OBJECTIVE: To investigate the prevalence of PLA2R1 in renal biopsy specimens of patients with idiopathic membranous nephropathy (IMN) and explore the relationship between PLA2R1 and IMN. METHODS: A total of 108 adult patients with biopsy-proved glomerular diseases were enrolled in this study, including 41 with IMN, 2 with hepatitis B-associated membranous nephropathy, 8 with V lupus nephritis, 27 with IgA nephropathy, 19 with minimal change nephropathy, 5 with mild mesangial proliferative glomerulonephritis, and 6 with focal segmental glomeruloselerosis (FSGS). Indirect immunofluorescence assay was used to detect PLA2R1 in the biopsy specimens and the clinical variables of the IMN patients were analyzed. RESULTS: In 35 of the 41 (85.37%) patients with IMN, PLA2R1 was detected with a fine granular pattern in the subepithelial deposits along the glomerular capillary loops. PLA2R1 antigen was not detected in patients with other glomerulopathies. No significant differences were found in age, serum creatinine, serum albumin, or 24-h urinary protein level between PLA2R1-positive and negative patients with IMN (P>0.05). CONCLUSION: According to our results, 85.37% of adult patients with biopsy-proven IMN are positive for PLA2R1 antigen, which, however, does not contribute to variations of the patients' clinical manifestations.

Prevalence and distribution of metabolic syndrome in a southern Chinese population. Relation to exercise, smoking, and educational level.

OBJECTIVE: To investigate the prevalence and distribution of metabolic syndrome (MetS) and the impact of exercise, smoking, and educational level on the risk of MetS in a southern Chinese population. METHODS: A cross-sectional study was conducted in Zhuhai City, China from June to August 2012. Data on exercise, smoking, and educational level, anthropometric parameters, blood pressure, lipid, and glucose levels were collected. The prevalence of MetS (as defined by the International Diabetes Federation) was determined. Data necessary to evaluate MetS, the socio-economic characteristics, and lifestyle were obtained for 4645 subjects aged 18-75 years old. RESULTS: A total of 19.8% of the participants had MetS. The adjusted odds of having MetS were lower among males (adjusted odds: 0.75; 95% confidence interval [CI]: 0.57-1.01) compared with females. Those participants who currently smoked had a higher risk of developing MetS compared with non-smokers (adjusted odds: 1.61; 95% CI: 1.13-2.50). Those who had no physical exercise had a higher risk of developing MetS compared with those who physically exercised more than 60 minutes/day (adjusted odds: 1.51; 95% CI: 1.12-2.23;). Compared with those with no education, every category of attained educational level had a lower risk of developing MetS (p<0.001). CONCLUSION: The findings in this study revealed that current smokers had a greater risk of developing MetS compared with non-smokers. Increased physical activity and higher levels of education attained served as protective factors for the population.

Prevalence of chronic kidney disease and prediabetes and associated risk factors: a community-based screening in Zhuhai, Southern China.

BACKGROUND: The prevalence of chronic kidney disease (CKD) and prediabetes has increased in China, and at different rates in different locations. Therefore a community-based screening research was conducted in order to determine the prevalence of CKD and prediabetes, and to analyze associated risk factors of CKD and prediabetes in a city of Southern China. METHODS: A total of 7801 community residents aged 18 year and older from 6 communities were screened by a stratified random cluster sampling method. An estimated glomerular filtration rate (eGFR), albuminuria, fasting plasma glucose (FPG), and homeostatic model assessment of insulin resistance (HOMA-IR) were measured. Age-standardized prevalence was calculated by the direct method with the use of data on the population distribution in China in 2006. Multivariate logistic analysis was used to analyze the risk factors of CKD and prediabetes, and association of insulin resistance (IR) with CKD and prediabetes was analyzed. RESULTS: The age-standardized prevalence of CKD was 12.5%, eGFR < 60 ml×min(-1)×1.73 m(-2) was 2.7% and ACR (albumin to creatinine ratio) > 30 mg/g was 10.3%. The age-standardized prevalence of prediabetes was 12.1%. Logistic regression suggests that IR was a common independent risk factor of CKD and prediabetes. Further analysis show that HOMA-IR was increased with the aggravation of kidney injury and FPG. CONCLUSION: CKD and prediabetes have become a major public health problem in Zhuhai, Southern China; insulin resistance may be an important risk factor.

[Expression of MMP-2 and TIMP-1 in renal tissues of patients with chronic active antibody-mediated renal graft rejection].

OBJECTIVE: To investigate the expressions of matrix metalloprotein-2 (MMP-2) and tissue inhibitor of metallopeptidase inhibitor-1 (TIMP-1) in the renal allografts of patients with chronic active antibody-mediated rejection (ABMR), and explore their role in the pathogenesis of ABMR. METHODS: Immunohistochemistry and computer-assisted image analysis were used to detect the expression of MMP-2 and TIMP-1 in the renal allografts of 46 patients with interstitial fibrosis and tubular atrophy (IF/TA), with 15 normal renal tissue specimens as the control. The association of MMP-2 and TIMP-1 with the pathological grade of IF/TA in ABMR was analyzed. RESULTS: The expressions of MMP-2 and TIMP-1 significantly increased in the renal tissues of the patients as compared with the normal renal tissues (P<0.05). MMP-2 expression tended to decrease, while TIMP-1 and serum creatinine increased with the pathological grades of IF/TA (P<0.05). In IF/TA group, the expression of TIMP-1 was positively correlated to serum creatinine level (r=0.718, P=0.00<0.05). CONCLUSION: Abnormal expressions of MMP-2 and TIMP-1 can promote the development of renal fibrosis in chronic ABMR.

Anti-SARS-CoV immunoglobulin G in healthcare workers, Guangzhou, China.

To determine the prevalence of inapparent infection with severe acute respiratory syndrome (SARS) among healthcare workers, we performed a serosurvey to test for immunoglobulin (Ig) G antibodies to the SARS coronavirus (SARS-CoV) among 1,147 healthcare workers in 3 hospitals that admitted SARS patients in mid-May 2003. Among them were 90 healthcare workers with SARS. As a reference group, 709 healthcare workers who worked in 2 hospitals that never admitted any SARS patients were similarly tested. The seroprevalence rate was 88.9% (80/90) for healthcare workers with SARS and 1.4% (15/1,057) for healthcare workers who were apparently healthy. The seroprevalence in the reference group was 0.4% (3/709). These findings suggest that inapparent infection is uncommon. Low level of immunity among unaffected healthcare workers reinforces the need for adequate personal protection and other infection control measures in hospitals to prevent future epidemics.